Confronting false discoveries in single-cell differential expression

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 28, 2021

Differential expression analysis in single-cell transcriptomics enables the dissection of cell-type-specific responses to perturbations such as disease, trauma, or experimental manipulations. While many statistical methods are available identify differentially expressed genes, principles that distinguish these and their performance remain unclear. Here, we show relative is contingent on ability account for variation between biological replicates. Methods ignore this inevitable biased prone false discoveries. Indeed, most widely used can discover hundreds genes absence differences. To exemplify principles, exposed true discoveries injured mouse spinal cord.

Language: Английский

---

Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury

Neuron, Journal Year: 2020, Volume and Issue: 108(1), P. 128 - 144.e9

Published: Aug. 17, 2020

Language: Английский

---

Mouse Retinal Cell Atlas: Molecular Identification of over Sixty Amacrine Cell Types

Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 40(27), P. 5177 - 5195

Published: May 26, 2020

Amacrine cells (ACs) are a diverse class of interneurons that modulate input from photoreceptors to retinal ganglion (RGCs), rendering each RGC type selectively sensitive particular visual features, which then relayed the brain. While many AC types have been identified morphologically and physiologically, they not comprehensively classified or molecularly characterized. We used high-throughput single-cell RNA sequencing profile >32,000 ACs mice both sexes applied computational methods identify 63 types. molecular markers for them characterize morphology multiple show include nearly all previously known as well had described. Consistent with previous studies, most expressed canonical inhibitory neurotransmitters GABA glycine, but several neither both. In addition, one more neuropeptides, two glutamatergic markers. also explored transcriptomic relationships among transcription factors by individual closely related Noteworthy these were Meis2 Tcf4, GABAergic glycinergic types, respectively. Together, results provide foundation developmental functional studies ACs, means genetically accessing them. Along molecular, physiological, morphologic analyses, establish existence at least 130 neuronal 140 cell in mouse retina. SIGNIFICANCE STATEMENT The retina is leading model analyzing development, structure, function, pathology neural circuits. A complete atlas provides an important studies. heterogeneous interneurons, amacrine cells, identifying distinct includes novel evidence use groups Combining those obtained previously, we proposed contains ∼130 therefore comparable complexity other regions

Language: Английский

---

Single-Cell Analysis of Human Retina Identifies Evolutionarily Conserved and Species-Specific Mechanisms Controlling Development

Developmental Cell, Journal Year: 2020, Volume and Issue: 53(4), P. 473 - 491.e9

Published: May 1, 2020

Language: Английский

---

Solving neurodegeneration: common mechanisms and strategies for new treatments

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: March 21, 2022

Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology site disease pathology. To address these and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus the Melza M. Frank Theodore Barr Foundation collaborated to bring together key opinion leaders experts field for a virtual meeting titled "Solving Neurodegeneration". This "think-tank" style focused uncovering mechanistic roots promising new catalyzed by goal finding treatments glaucoma, world's leading cause irreversible blindness interest three hosting foundations. Glaucoma, which causes vision loss through degeneration optic nerve, likely shares early cellular molecular events with other diseases central nervous system. Here we major areas overlap between system: neuroinflammation, bioenergetics metabolism, genetic contributions, neurovascular interactions. We summarize important discussion points emphasis research that are most innovative treatment neurodegeneration yet require further development. The is highlighted provides unique opportunities collaboration will lead efforts preventing ultimately loss.

Language: Английский

---

Neurotoxic Reactive Astrocytes Drive Neuronal Death after Retinal Injury

Cell Reports, Journal Year: 2020, Volume and Issue: 31(12), P. 107776 - 107776

Published: June 1, 2020

Glaucoma is a neurodegenerative disease that features the death of retinal ganglion cells (RGCs) in retina, often as result prolonged increases intraocular pressure. We show preventing formation neuroinflammatory reactive astrocytes prevents RGCs normally seen mouse model glaucoma. Furthermore, we these spared are electrophysiologically functional and thus still have potential value for function regeneration retina. Finally, demonstrate depends on combination both an injury to neurons presence astrocytes, suggesting may explain why toxic only some circumstances. Altogether, findings highlight drivers RGC chronic eye.

Language: Английский

---

Unified classification of mouse retinal ganglion cells using function, morphology, and gene expression

Cell Reports, Journal Year: 2022, Volume and Issue: 40(2), P. 111040 - 111040

Published: July 1, 2022

Classification and characterization of neuronal types are critical for understanding their function dysfunction. Neuronal classification schemes typically rely on measurements electrophysiological, morphological, molecular features, but aligning such datasets has been challenging. Here, we present a unified mouse retinal ganglion cells (RGCs), the sole output neurons. We use visually evoked responses to classify 1,859 RGCs into 42 types. also obtain morphological or transcriptomic data from subsets these align functional publicly available datasets. create an online database that allows users browse download light using machine learning algorithm. This work provides resource studies RGCs, upstream circuits in retina, projections brain, establishes framework future efforts open distribution.

Language: Английский

---

Central nervous system regeneration

Cell, Journal Year: 2022, Volume and Issue: 185(1), P. 77 - 94

Published: Jan. 1, 2022

Language: Английский

---

Jointly defining cell types from multiple single-cell datasets using LIGER

Nature Protocols, Journal Year: 2020, Volume and Issue: 15(11), P. 3632 - 3662

Published: Oct. 12, 2020

Language: Английский

---

Axon Regeneration in the Mammalian Optic Nerve

Annual Review of Vision Science, Journal Year: 2020, Volume and Issue: 6(1), P. 195 - 213

Published: Sept. 15, 2020

The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, compressive optic neuropathies from glioma. By using nerve crush injury models, recent studies have revealed cellular molecular logic behind regenerative failure injured RGC adult mammals suggested several strategies with translational potential. This review summarizes these findings discusses challenges developing clinically applicable neural repair strategies.

Language: Английский

---